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CompletedNCT00300781Updated Aug 14, 2018Results posted

Study Evaluating HKI-272 (Neratinib) In Subjects With Advanced Breast Cancer

A Phase 2 interventional study of neratinib in Breast Neoplasms and Neoplasms, sponsored by Puma Biotechnology, Inc.. Completed at 33 sites in 7 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-14.

Sponsored by Puma Biotechnology, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
136
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

The purpose of this study is to learn whether neratinib is safe and effective in treating women with advanced human epidermal growth factor receptor 2 (HER2) positive breast cancer.

Read the detailed description

Arm A: HER2 gene amplification and disease progression following at least 6 weeks of standard doses of Herceptin; Arm B: HER2 gene amplification and no prior Herceptin or HER2-targeted treatment.

02

Conditions studied

  • Breast Neoplasms
  • Neoplasms

Keywords

  • phase 2
  • HER2+ breast cancer
  • monotherapy neratinib
  • HKI-272
  • Neratinib
  • Nerlynx
  • PB-272
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 136 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Puma Biotechnology, Inc. is the lead sponsor of 38 studies on the registry; 3 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV
  • Progression following at least 6 weeks of standard doses of Herceptin (Arm A only)
  • Over-expression of HER2
  • Tumor tissue available and adequate for analysis at screening
  • At least one measurable lesion

Exclusion criteria

Exclusion Criteria:

  • Prior treatment with Herceptin (Arm B only)
  • More than 4 prior cytotoxic chemotherapy regimens
  • Subjects with bone or skin as the only site of measurable disease
  • Inadequate cardiac function
  • Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 1 week of treatment day 1
  • Active central nervous system metastases
  • Pregnant or breastfeeding women
  • Inability to swallow the HKI-272 capsules
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
136 participants (actual)

Study arms

  • Experimental
    Neratinib 240 mg, with prior trastuzumab

    Neratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen.

    Drug: neratinib

  • Experimental
    Neratinib 240 mg, no prior trastuzumab

    Neratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen.

    Drug: neratinib

Interventions

  • Drugneratinib

    Also known as: Nerlynx, HKI-272

06

What researchers measure

Primary outcomes

  1. 16-week Progression Free Survival

    16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks.

    Time frame: From first dose to 16 weeks

Secondary outcomes

  1. Objective Response Rate

    Percentage of participants with Partial Response (PR) or Complete Response (CR) by independent assessment of tumor per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Time frame: From first dose date to progression or last tumor assessment, up to 46 months

  2. Clinical Benefit Rate

    Percentage of participants who experienced Complete Response (CR), Partial Response (PR), or Stable Disease (SD) ≥ 24 weeks by independent assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

    Time frame: From first dose date to progression or last tumor assessment, up to 46 months

  3. Duration of Response

    Number of weeks between Complete Response (CR) or Partial Response (PR) and the first date of disease progression (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions

    Time frame: From start date of response to first PD/death, up to 46 months

07

Results

Posted Sep 13, 2017

Participant flow

Participant flow — Overall Study
MilestoneNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
Started6670
Completed38
Not completed6362
Withdrew: Disease progression5552
Withdrew: Adverse event56
Withdrew: Withdrawal by subject12
Withdrew: Physician decision10
Withdrew: Not recorded01
Withdrew: Symptomatic deterioration10
Withdrew: Lost to follow-up01

Outcome measures

Primary16-week Progression Free Survival

16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks.

Time frame:
From first dose to 16 weeks
Reported as:
Number · percentage of participants
16-week Progression Free Survival
percentage of participantsNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
16-week Progression Free Survival58.2 (45.3 to 71.2)77.8 (67.6 to 88.1)
SecondaryObjective Response Rate

Percentage of participants with Partial Response (PR) or Complete Response (CR) by independent assessment of tumor per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Time frame:
From first dose date to progression or last tumor assessment, up to 46 months
Reported as:
Number · percentage of participants
Objective Response Rate
percentage of participantsNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
Objective Response Rate24.2 (14.5 to 36.4)52.9 (40.6 to 64.9)
SecondaryClinical Benefit Rate

Percentage of participants who experienced Complete Response (CR), Partial Response (PR), or Stable Disease (SD) ≥ 24 weeks by independent assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Time frame:
From first dose date to progression or last tumor assessment, up to 46 months
Reported as:
Number · percentage of participants
Clinical Benefit Rate
percentage of participantsNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
Clinical Benefit Rate31.8 (20.9 to 44.4)62.9 (50.5 to 74.1)
SecondaryDuration of Response

Number of weeks between Complete Response (CR) or Partial Response (PR) and the first date of disease progression (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions

Time frame:
From start date of response to first PD/death, up to 46 months
Reported as:
Median · weeks
Duration of Response
weeksNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
Duration of Response40.3 (32.3 to 80.1)60.0 (40.1 to 100.1)

Adverse events

Collected over From first dose through 28 days after last dose, up to 46 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Neratinib 240, Prior Trastuzumab—19/66 (28.8%)66/66 (100%)
Neratinib 240, No Prior Trastuzumab—17/70 (24.3%)70/70 (100%)
Most frequent serious events
Showing 10 of 40
Most frequent serious events
EventNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
VomitingGastrointestinal disorders3/666/70
DiarrhoeaGastrointestinal disorders4/664/70
DehydrationMetabolism and nutrition disorders2/664/70
NauseaGastrointestinal disorders2/660/70
Decreased appetiteMetabolism and nutrition disorders2/661/70
NephrolithiasisRenal and urinary disorders2/660/70
DyspnoeaRespiratory, thoracic and mediastinal disorders2/661/70
Pleural effusionRespiratory, thoracic and mediastinal disorders2/661/70
FatigueGeneral disorders1/660/70
SinusitisInfections and infestations1/660/70
Most frequent other events
Showing 10 of 46
Most frequent other events
EventNeratinib 240, Prior TrastuzumabNeratinib 240, No Prior Trastuzumab
DiarrhoeaGastrointestinal disorders63/6664/70
NauseaGastrointestinal disorders27/6623/70
FatigueGeneral disorders26/667/70
VomitingGastrointestinal disorders16/6623/70
Abdominal painGastrointestinal disorders19/666/70
Decreased appetiteMetabolism and nutrition disorders15/6612/70
RashSkin and subcutaneous tissue disorders14/669/70
HeadacheNervous system disorders12/6614/70
PyrexiaGeneral disorders5/6612/70
AstheniaGeneral disorders3/6610/70

Baseline characteristics

All treated subjects

Age, Continuous
Age, Continuous(years)Neratinib 240, Prior TrastuzumabNeratinib 240, No Prior TrastuzumabTotal
Mean51.62 ± 10.6749.64 ± 9.9250.60 ± 10.30
Sex: Female, Male
Sex: Female, Male(Participants)Neratinib 240, Prior TrastuzumabNeratinib 240, No Prior TrastuzumabTotal
Female6670136
Male000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Neratinib 240, Prior TrastuzumabNeratinib 240, No Prior TrastuzumabTotal
American Indian or Alaska Native000
Asian65258
Native Hawaiian or Other Pacific Islander000
Black or African American202
White551570
More than one race000
Unknown or Not Reported336
08

Study locations

33 sites
  • University of Colorado Hospital
    Aurora, Colorado 80045, United States
  • Midwestern Regional Medical Center
    Zion, Illinois 60099, United States
  • Louisiana State University
    Shreveport, Louisiana 71103, United States
  • The Cancer Center at GBMC
    Baltimore, Maryland 21204, United States
  • Oncology Care Associates
    Bethesda, Maryland 20817, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02115, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Boston University Medical Center
    Boston, Massachusetts 02118, United States
  • Faulkner Hospital
    Boston, Massachusetts 02130, United States
  • Norris Cotton Cancer Center Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
  • The Cancer Institute of New Jersey
    New Brunswick, New Jersey 08901, United States
  • The Cleveland Clinic Taussig Cancer Center
    Cleveland, Ohio 44195, United States
  • Virginia Mason Medical Center
    Seattle, Washington 98101, United States
  • Institut Jules Bordet Unite du Chimiotherapie
    Brussels, 1000, Belgium
  • University Hospital Gasthuisberg
    Leuven, 3000, Belgium
  • St-Augustinus Ziekenhuis Oncology Department
    Wilrijk, 2610, Belgium
  • The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
    Beijing, Beijing 100071, China
  • No. 81 Hospital of Chinese People's Liberation Army
    Nanjing, Jiangsu 210002, China
  • Cancer Hospital Peking Union Medical College
    Beijing, 100021, China
  • Chinese People's Liberation Army General Hospital
    Beijing, 100853, China
  • Institut Gustave ROUSSY Service de Pathologie Mammaire
    Villejuif Cedex, 94805, France
  • Jehangir Clinical Development Centre
    Pune, Maharashtra 411001, India
  • Deenanath Mangeshkar Hospital
    Pune, Maharashtra 411004, India
  • Nizam's Institute of Medical Sciences
    Hyderabad, Panjagutta 50082, India
  • Tata Memorial Centre
    Mumbai, Parel 400012, India
  • Hospital Regional Lic. Adolfo Lopez Mateos Oncología Médica
    Mexico City, 01030, Mexico
  • Arke Estudios Clínicos S.A. de C.V.
    Mexico City, 06700, Mexico
  • Hospital de Especialidades MIG
    Mexico City, 07300, Mexico
  • N.N. Blokhin Russian Cancer Research Center of RAMS
    Moscow, 115478, Russian Federation
  • Medical Radiological Research Center of RAMS, Department of Radiation and Surgical Methods
    Obninsk, 249036, Russian Federation
  • City Oncology Dispensary
    Saint Petersburg, 197022, Russian Federation
  • City Hospital N 31 Oncology Haematology Dept. For Adults
    Saint Petersburg, 197110, Russian Federation
  • Breast Tumor Department, N.N. Petrov Research Institute of Oncology
    Saint-Petersburg, 197758, Russian Federation
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 14, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00300781
Lead sponsor
Puma Biotechnology, Inc.
Responsible party
Sponsor
First posted
Mar 9, 2006
Start date
Aug 4, 2006
Primary completion
Apr 2008
Completion
Jan 30, 2018
Results posted
Sep 13, 2017
Last update
Aug 14, 2018

Study contacts

Puma
study director · Biotechnology

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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